Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.

Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).

Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

Therapeutics targeting frontotemporal dementia (FTD) are entering clinical trials. There are challenges to conducting these studies, including the relative rarity of the disease. Remote assessment tools could increase access to clinical research and pave the way for decentralized clinical trials. We developed the ALLFTD Mobile App, a smartphone application that includes assessments of cognition, speech/language, and motor functioning. The objectives were to determine the feasibility and acceptability of collecting remote smartphone data in a multicenter FTD research study and evaluate the reliability and validity of the smartphone cognitive and motor measures.

A diagnostically mixed sample of 207 participants with FTD or from familial FTD kindreds (CDR®+NACC-FTLD=0 [n=91]; CDR®+NACC-FTLD=0.5 [n=39]; CDR®+NACC-FTLD>1 [n=39]; unknown [n=38]) were asked to remotely complete a battery of tests on their smartphones three times over two weeks. Measures included five executive functioning (EF) tests, an adaptive memory test, and participant experience surveys. A subset completed smartphone tests of balance at home (n=31) and a finger tapping test (FTT) in the clinic (n=11). We analyzed adherence (percentage of available measures that were completed) and user experience. We evaluated Spearman-Brown split-half reliability (100 iterations) using the first available assessment for each participant. We assessed test-retest reliability across all available assessments by estimating intraclass correlation coefficients (ICC). To investigate construct validity, we fit regression models testing the association of the smartphone measures with gold-standard neuropsychological outcomes (UDS3-EF composite [Staffaroni et al., 2021], CVLT3-Brief Form [CVLT3-BF] Immediate Recall, mechanical FTT), measures of disease severity (CDR®+NACC-FTLD Box Score & Progressive Supranuclear Palsy Rating Scale [PSPRS]), and regional gray matter volumes (cognitive tests only).

Participants completed 70% of tasks. Most reported that the instructions were understandable (93%), considered the time commitment acceptable (97%), and were willing to complete additional assessments (98%). Split-half reliability was excellent for the executive functioning (r’s=0.93-0.99) and good for the memory test (r=0.78). Test-retest reliabilities ranged from acceptable to excellent for cognitive tasks (ICC: 0.70-0.96) and were excellent for the balance (ICC=0.97) and good for FTT (ICC=0.89). Smartphone EF measures were strongly associated with the UDS3-EF composite (ß's=0.6-0.8, all p<.001), and the memory test was strongly correlated with total immediate recall on the CVLT3-BF (ß=0.7, p<.001). Smartphone FTT was associated with mechanical FTT (ß=0.9, p=.02), and greater acceleration on the balance test was associated with more motor features (ß=0.6, p=0.02). Worse performance on all cognitive tests was associated with greater disease severity (ß's=0.5-0.7, all p<.001). Poorer performance on the smartphone EF tasks was associated with smaller frontoparietal/subcortical volume (ß's=0.4-0.6, all p<.015) and worse memory scores with smaller hippocampal volume (ß=0.5, p<.001).

These results suggest remote digital data collection of cognitive and motor functioning in FTD research is feasible and acceptable. These findings also support the reliability and validity of unsupervised ALLFTD Mobile App cognitive tests and provide preliminary support for the motor measures, although further study in larger samples is required.

Approximately 73% of the United States (US) population on public water systems receives fluoridated water for tooth decay prevention. In Los Angeles (LA) County, 89% of cities are at least partially fluoridated. Drinking water is the primary source of fluoride exposure in the US. Studies conducted in Mexico and Canada suggest that prenatal fluoride exposure, at levels relevant to the US, may contribute to poorer neurodevelopment in offspring. However, data on biomarkers and patterns of fluoride exposure among US pregnant women are scarce. This study examined urinary fluoride levels according to sociodemographic factors and metal co-exposures among pregnant women in the US.

Participants were from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort based in Los Angeles, California. There were 293 and 490 women with urine fluoride measured during the first and third trimesters of pregnancy, respectively. An intra-class correlation coefficient examined consistency of specific gravity-adjusted maternal urinary fluoride (MUFsg) between trimesters. Kruskal-Wallis and Mann-Whitney U tests examined associations of MUFsg with sociodemographic variables. Spearman correlations examined associations of MUFsg with blood and urine metals within and between trimesters. A False Discovery Rate (FDR) correction accounted for multiple comparisons. The criterion for statistical significance was an alpha of 0.05.

Participants were approximately 29 years old on average, and 80% were Hispanic or Latina. Median (IQR) MUFsg during trimesters one and three was 0.65 (0.5) mg/L and 0.8 (0.59) mg/L, respectively. MUFsg levels were moderately consistent between trimesters (N=292, ICC = 0.46, 95%CI: 0.32,0.57). Maternal age was positively associated with MUFsg during first (p = 0.16, p = 0.006) and third (p = 0.18, p < 0.001) trimesters. MUFsg differed by race/ethnicity during first and third trimesters (N = 293, H (3) = 7.99, p = 0.046; N = 486, H (3) = 25.31, p < 0.001, respectively). Specifically, MUFsg was higher for White, Non-Hispanic participants (first trimester Median (IQR) =1.03 (1.31) mg/L; third trimester Median (IQR) = 1.32 (1.24) mg/L) than for Hispanic participants in both trimesters (first trimester Median (IQR) =0.64 (0.48) mg/L; third trimester Median (IQR) = 0.76 (0.55) mg/L). Additionally, during trimester three, MUFsg was higher for White, Non-Hispanic participants than for Black Non-Hispanic participants (Median (IQR) = 0.82 (0.49) mg/L). MUFsg also differed by education during trimester one (N = 293, H (4) = 10.61, p = 0.031), and was higher for participants with some graduate training than for those with high school or some college/technical school education (ps = 0.03 and 0.04, respectively). After FDR correction, MUFsg was associated with blood lead (N =91, p = 0.29, p = 0.024) and urinary cadmium (N =279, p = 0.19, p = 0.042), copper (N=279, p = 0.16, p = 0.042), and tungsten (N=279, p = 0.16, p = 0.049) during trimester three.

Consistent with studies conducted in Canada and Mexico, MUFsg increased across pregnancy. Lower MUFsg among Hispanic and Non-Hispanic Black participants may reflect lower tap water consumption. Metal co-exposures are important to consider when examining potential neurodevelopmental impacts of fluoride.

This study aimed to investigate mother–infant interaction and infant development in women at-risk of postpartum psychosis (PP), with and without a postpartum relapse.

103 women (and their offspring) were included, 43 at-risk-of-PP because of a diagnosis of bipolar disorder, schizoaffective disorder or previous PP, and 60 with no current/previous mental illness or family history of PP. Of the at-risk women, 18 developed a psychiatric relapse within 4 weeks after delivery (AR-unwell), while 25 remained symptom-free (AR-well). Mother–infant interaction was assessed using the CARE-Index at 8 weeks' and 12 months' postpartum and infant development using the Bayley-III at 12 months' postpartum.

Women at-risk-of-PP as a group, regardless of whether they developed a psychiatric relapse within 4 weeks after delivery, had less synchronous mother–infant interactions and had infants with less optimal cognitive, language, motor and socio-emotional development than healthy controls. In particular, boys of at-risk women had the lowest scores in cognitive, language and motor development and in mother–infant interaction, while girls of the at-risk women had the lowest scores in socio-emotional development. The synchrony in the dyad predicted infant cognitive and language development. There was no evidence for a difference in mother–infant interaction nor in infant development between the AR-unwell and AR-well groups.

These results suggest that, while there is a lack of evidence that an early postpartum relapse in women at-risk-of-PP could represent a risk for the infant per se, maternal risk for PP may be associated with less optimal mother–infant interaction and infant development.

Although COVID-19 is known to have cardiac effects in children, seen primarily in severe disease, more information is needed about the cardiac effects following COVID-19 in non-hospitalised children and adolescents during recovery. This study aims to compare echocardiographic markers of cardiac size and function of children following acute COVID-19 with those of healthy controls.

This single-centre retrospective case–control study compared 71 cases seen in cardiology clinic following acute COVID-19 with 33 healthy controls. Apical left ventricle, apical right ventricle, and parasternal short axis at the level of the papillary muscles were analysed to measure ventricular size and systolic function. Strain was analysed on vendor-independent software. Statistical analysis was performed using t-test, chi-square, Wilcoxon rank sum, and regression modelling as appropriate (p < 0.05 significant).

Compared to controls, COVID-19 cases had slightly higher left ventricular volumes and lower left ventricular ejection fraction and right ventricular fractional area change that remained within normal range. There were no differences in right or left ventricular longitudinal strain between the two groups. Neither initial severity nor persistence of symptoms after diagnosis predicted these differences.

Echocardiographic findings in children and adolescents 6 weeks to 3 months following acute COVID-19 not requiring hospitalisation were overall reassuring. Compared to healthy controls, the COVID-19 group demonstrated mildly larger left ventricular size and lower conventional measures of biventricular systolic function that remained within the normal range, with no differences in biventricular longitudinal strain. Future studies focusing on longitudinal echocardiographic assessment of patients following acute COVID-19 are needed to better understand these subtle differences in ventricular size and function.

Despite emerging evidence suggesting the efficacy of psilocybin in the treatment of mood disorders such as depression, the exact mechanisms by which psilocybin is able to elicit these antidepressant effects remains unknown.

As the use of psilocybin as a treatment modality for depression has garnered increasing interest, this study aims to summarize the existing evidence of the mechanism of action with which psilocybin alleviates depressive symptoms, focusing specifically on the neurobiological effects of psilocybin in human subjects.

Four databases (Ovid MEDLINE, EMBASE, psychINFO, and Web of Science) were searched using a combination of MeSH terms and free text keywords in September 2021. The original search included both human and animal studies and must have included testing of the mechanism of action of psilocybin. Only antidepressant effects were considered, with no other mood disorders or psychiatric diagnoses included. Two independent researchers screened at every stage of the review, with a third researcher resolving any conflicts. Though a full systematic review outlining the current literature on the complete mechanisms of action of psilocybin on depression was conducted, this abstract will focus specifically on the nine papers that included human subjects, disregarding the five animal models. PROSPERO registration number: 282710.

After removing duplicates, the search identified 2193 papers and forty-nine were selected for full text review. Out of nine papers outlining the mechanisms of action of psilocybin use in human subjects, three papers investigated psilocybin’s effect on serotonin or glutamate receptor activity, two found an increase in synaptogenesis in regions such as the medial frontal cortex and hippocampus. Four found variation in blood flow to the amygdala, two found altered blood flow to the prefrontal cortex, and one found a reduction in delta power during sleep. Four papers found changes in functional connectivity or neurotransmission, most commonly in the hippocampus or prefrontal cortex.

Overall, the exact mechanism of psilocybin’s potential antidepressant effect remains unclear. Multiple pathways may be involved, including alterations in serotonin and glutamate receptor activity, as well as shifts in amygdala activity, neurogenesis, and functional connectivity in various brain regions. The relative lack of studies, and the variety of neurobiological modalities and endpoints used challenged the consolidation of data into consensus findings. Further studies are needed to better characterize psilocybin’s mechanism of action and to better understand the clinical effects of the use of psilocybin in the treatment of depression.

None Declared

Researchers have identified genetic and neural risk factors for externalizing behaviors. However, it has not yet been determined if genetic liability is conferred in part through associations with more proximal neurophysiological risk markers.

Participants from the Collaborative Study on the Genetics of Alcoholism, a large, family-based study of alcohol use disorders were genotyped and polygenic scores for externalizing (EXT PGS) were calculated. Associations with target P3 amplitude from a visual oddball task (P3) and broad endorsement of externalizing behaviors (indexed via self-report of alcohol and cannabis use, and antisocial behavior) were assessed in participants of European (EA; N = 2851) and African ancestry (AA; N = 1402). Analyses were also stratified by age (adolescents, age 12–17 and young adults, age 18–32).

The EXT PGS was significantly associated with higher levels of externalizing behaviors among EA adolescents and young adults as well as AA young adults. P3 was inversely associated with externalizing behaviors among EA young adults. EXT PGS was not significantly associated with P3 amplitude and therefore, there was no evidence that P3 amplitude indirectly accounted for the association between EXT PGS and externalizing behaviors.

Both the EXT PGS and P3 amplitude were significantly associated with externalizing behaviors among EA young adults. However, these associations with externalizing behaviors appear to be independent of each other, suggesting that they may index different facets of externalizing.

Only a limited number of patients with major depressive disorder (MDD) respond to a first course of antidepressant medication (ADM). We investigated the feasibility of creating a baseline model to determine which of these would be among patients beginning ADM treatment in the US Veterans Health Administration (VHA).

A 2018–2020 national sample of n = 660 VHA patients receiving ADM treatment for MDD completed an extensive baseline self-report assessment near the beginning of treatment and a 3-month self-report follow-up assessment. Using baseline self-report data along with administrative and geospatial data, an ensemble machine learning method was used to develop a model for 3-month treatment response defined by the Quick Inventory of Depression Symptomatology Self-Report and a modified Sheehan Disability Scale. The model was developed in a 70% training sample and tested in the remaining 30% test sample.

In total, 35.7% of patients responded to treatment. The prediction model had an area under the ROC curve (s.e.) of 0.66 (0.04) in the test sample. A strong gradient in probability (s.e.) of treatment response was found across three subsamples of the test sample using training sample thresholds for high [45.6% (5.5)], intermediate [34.5% (7.6)], and low [11.1% (4.9)] probabilities of response. Baseline symptom severity, comorbidity, treatment characteristics (expectations, history, and aspects of current treatment), and protective/resilience factors were the most important predictors.

Although these results are promising, parallel models to predict response to alternative treatments based on data collected before initiating treatment would be needed for such models to help guide treatment selection.

Racial disparities in colorectal cancer (CRC) can be addressed through increased adherence to screening guidelines. In real-life encounters, patients may be more willing to follow screening recommendations delivered by a race concordant clinician. The growth of telehealth to deliver care provides an opportunity to explore whether these effects translate to a virtual setting. The primary purpose of this pilot study is to explore the relationships between virtual clinician (VC) characteristics and CRC screening intentions after engagement with a telehealth intervention leveraging technology to deliver tailored CRC prevention messaging.

Using a posttest-only design with three factors (VC race-matching, VC gender, intervention type), participants (N = 2267) were randomised to one of eight intervention treatments. Participants self-reported perceptions and behavioral intentions.

The benefits of matching participants with a racially similar VC trended positive but did not reach statistical significance. Specifically, race-matching positively influenced screening intentions for Black participants but not for Whites (b = 0.29, p = 0.10). Importantly, perceptions of credibility, attractiveness, and message relevance significantly influenced screening intentions and the relationship with race-matching.

To reduce racial CRC screening disparities, investments are needed to identify patient-focused interventions to address structural barriers to screening. This study suggests that telehealth interventions that match Black patients with a Black VC can enhance perceptions of credibility and message relevance, which may then improve screening intentions. Future research is needed to examine how to increase VC credibility and attractiveness, as well as message relevance without race-matching.

Fewer than half of patients with major depressive disorder (MDD) respond to psychotherapy. Pre-emptively informing patients of their likelihood of responding could be useful as part of a patient-centered treatment decision-support plan.

This prospective observational study examined a national sample of 807 patients beginning psychotherapy for MDD at the Veterans Health Administration. Patients completed a self-report survey at baseline and 3-months follow-up (data collected 2018–2020). We developed a machine learning (ML) model to predict psychotherapy response at 3 months using baseline survey, administrative, and geospatial variables in a 70% training sample. Model performance was then evaluated in the 30% test sample.

32.0% of patients responded to treatment after 3 months. The best ML model had an AUC (SE) of 0.652 (0.038) in the test sample. Among the one-third of patients ranked by the model as most likely to respond, 50.0% in the test sample responded to psychotherapy. In comparison, among the remaining two-thirds of patients, <25% responded to psychotherapy. The model selected 43 predictors, of which nearly all were self-report variables.

Patients with MDD could pre-emptively be informed of their likelihood of responding to psychotherapy using a prediction tool based on self-report data. This tool could meaningfully help patients and providers in shared decision-making, although parallel information about the likelihood of responding to alternative treatments would be needed to inform decision-making across multiple treatments.

Understanding the cognitive determinants of healthcare worker (HCW) behavior is important for improving the use of infection prevention and control (IPC) practices. Given a patient requiring only standard precautions, we examined the dimensions along which different populations of HCWs cognitively organize patient care tasks (ie, their mental models).

HCWs read a description of a patient and then rated the similarities of 25 patient care tasks from an infection prevention perspective. Using multidimensional scaling, we identified the dimensions (ie, characteristics of tasks) underlying these ratings and the salience of each dimension to HCWs.

Adult inpatient hospitals across an academic hospital network.

In total, 40 HCWs, comprising infection preventionists and nurses from intensive care units, emergency departments, and medical-surgical floors rated the similarity of tasks. To identify the meaning of each dimension, another 6 nurses rated each task in terms of specific characteristics of tasks.

Each HCW population perceived patient care tasks to vary along 3 common dimensions; most salient was the perceived magnitude of infection risk to the patient in a task, followed by the perceived dirtiness and risk of HCW exposure to body fluids, and lastly, the relative importance of a task for preventing versus controlling an infection in a patient.

For a patient requiring only standard precautions, different populations of HCWs have similar mental models of how various patient care tasks relate to IPC. Techniques for eliciting mental models open new avenues for understanding and ultimately modifying the cognitive determinants of IPC behaviors.